Recombinant Human Serum Albumin Phase 1 AD (NCT06489015)

title: "Recombinant Human Serum Albumin Phase 1 AD (NCT06489015)"
description: Phase 1 open-label study of recombinant human serum albumin for mild to moderate Alzheimer disease
published: true
tags: section:clinical-trials, kind:clinical-trial, topic:alzheimers, state:published
editor: markdown

Recombinant Human Serum Albumin Phase 1 AD (NCT06489015)

Study Overview

NCT Number: NCT06489015

Official Title: Phase 1 Open-label, Exploratory Study of Recombinant Human Serum Albumin (rHSA) for Mild to Moderate Alzheimer's Disease

Study Type: Interventional (Phase 1)

Status: Recruiting

Study Start Date: June 2024

Estimated Enrollment: 30 participants

Background and Rationale

title: "Recombinant Human Serum Albumin Phase 1 AD (NCT06489015)"
description: Phase 1 open-label study of recombinant human serum albumin for mild to moderate Alzheimer disease
published: true
tags: section:clinical-trials, kind:clinical-trial, topic:alzheimers, state:published
editor: markdown

Recombinant Human Serum Albumin Phase 1 AD (NCT06489015)

Study Overview

NCT Number: NCT06489015

Official Title: Phase 1 Open-label, Exploratory Study of Recombinant Human Serum Albumin (rHSA) for Mild to Moderate Alzheimer's Disease

Study Type: Interventional (Phase 1)

Status: Recruiting

Study Start Date: June 2024

Estimated Enrollment: 30 participants

Background and Rationale

Human serum albumin is the most abundant plasma protein in the human body and plays multiple protective roles in systemic and brain health. Albumin binds and transports a wide variety of molecules, including:

• Fatty acids: Essential for neuronal energy metabolism
• Bilirubin: Potent endogenous antioxidant
• Drugs and hormones: Carrier for therapeutic compounds
• Metals: Binds copper, zinc, and other transition metals

The concept of using albumin as a therapeutic agent for AD is supported by:

• Observational studies showing lower serum albumin levels correlate with cognitive decline in AD
• Albumin replacement studies in other conditions showing neurological benefits
• Preclinical evidence of albumin-mediated neuroprotection

Study Objectives

Primary Objective

Secondary Objectives

Methods

Study Design

• Design: Single-arm, open-label, Phase 1 study
• Participants: 30 patients with mild to moderate AD (MMSE 12-26)
• Duration: 12-week treatment period with 4-week follow-up

Inclusion Criteria

• Age 50-85 years
• Diagnosis of probable AD (NIA-AA criteria)
• MMSE score 12-26 (mild to moderate dementia)
• Stable on AD medications (cholinesterase inhibitors, memantine) for ≥3 months
• Normal or stable medical conditions

Exclusion Criteria

• Other causes of dementia (vascular, Lewy body, frontotemporal)
• Active inflammatory or infectious disease
• Chronic liver disease (albumin synthesis impairment)
• Chronic kidney disease (albumin loss)
• Planned surgeries during study period

Treatment Regimen

| Parameter | Details |
|-----------|---------|
| Drug | Recombinant Human Serum Albumin (rHSA) |
| Dose | 1.5 g/kg (approximately 100g for average adult) |
| Route | Intravenous infusion |
| Frequency | Weekly infusions |
| Duration | 12 weeks (12 infusions total) |

Outcome Measures

Safety (Primary):

• Adverse event monitoring
• Vital signs
• Laboratory parameters (CBC, CMP, coagulation)
• Physical and neurological examinations

• Cognitive: ADAS-Cog13, MMSE, MoCA
• Functional: ADCS-ADL, CDR
• Behavioral: NPI, Neuropsychiatric Inventory
• Quality of Life: EQ-5D-5L

• CSF Aβ40, Aβ42, total tau, phosphorylated tau
• Plasma NfL, GFAP
• Serum albumin levels and albumin/globulin ratio

Scientific Rationale

Albumin-Aβ Interaction

Human serum albumin has been shown to:

• Bind Aβ monomers with moderate affinity
• Prevent Aβ fibril formation in vitro
• Reduce Aβ-induced neurotoxicity in cell culture
• Facilitate Aβ clearance through multiple mechanisms

Antioxidant Effects

Albumin's capacity to bind bilirubin makes it an important endogenous antioxidant:

• Bilirubin-albumin complexes neutralize reactive oxygen species
• Prevents lipid peroxidation in neuronal membranes
• May reduce 4-HNE and MDA levels in AD brain

Metal Chelation

Albumin's metal-binding properties may reduce redox-active metal catalysis of Aβ aggregation:

• Binds Cu²⁺ and Fe³⁺ with micromolar affinity
• Prevents metal-induced Aβ aggregation
• May reduce Fenton chemistry and oxidative damage

Relationship to Existing Knowledge

This trial connects to established mechanisms:

• [Amyloid-Beta Metabolism and Clearance](/mechanisms/amyloid-beta-metabolism)
• [Oxidative Stress in Alzheimer's](/mechanisms/oxidative-stress-ad)
• [Blood-Brain Barrier and CNS Drug Delivery](/mechanisms/bbb-dysfunction-pathway)
• [Metal Ion Dyshomeostasis in Neurodegeneration](/mechanisms/metal-ion-dyshomeostasis)

Expected Outcomes

Clinical Significance

If successful, rHSA therapy could provide:

• Novel mechanism: First-in-class approach targeting multiple pathways (Aβ, oxidative stress, metal dyshomeostasis)
• Accessibility: Well-characterized protein with established safety profile
• Combination potential: Could be combined with existing AD therapies
• Disease modification: Potential to address underlying pathophysiology

See Also

• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Amyloid-Beta Mechanisms](/mechanisms/amyloid-beta-metabolism)
• [Oxidative Stress Mechanisms](/mechanisms/oxidative-stress-ad)
• [Clinical Trials in Alzheimer's](/clinical-trials/)